Age-related changes in apolipoprotein A-I expression.

To determine the age-related changes in apolipoprotein A-I (ApoA1) expression, male Fischer 344 rats at 4 (young), 12 (intermediate age), and 24-26 (aged) months of age were studied. Immunoblot analysis of plasma proteins indicated that 26-month-old rats (1.79 +/- 0.16 mg/ml) and 12-month-old rats (2.23 +/- 0.11 mg/ml) have significantly higher plasma ApoA1 concentrations compared to 4-month-old rats (1.14 +/- 0.15 mg/ml) P < 0.001. Hepatic ApoA1 mRNA was approx. 2-fold higher in aged rats compared to 12-month-old and 4-month-old rats. This increase in hepatic ApoA1 mRNA in aged rats was also reflected in the increased translation of ApoA1 mRNA in vitro. Reduced mRNA turnover may account for the increased hepatic ApoA1 mRNA content in 26-month-old rats, since the rate of ApoA1 gene transcription as measured with nuclear run off assays was significantly reduced with age. The ApoA1 synthesis in vivo, as measured by [14C]leucine incorporation at 30 min, was reduced in aged rats compared to young rats (170.5 +/- 10.2 vs. 253.9 +/- 7.7 cpm per liver) P < 0.001 probably as a result of changes related to cellular metabolism rather than an alteration inherent to the ApoA1 mRNA translatability. The age-related increase in plasma ApoA1 protein is probably secondary to reduced metabolic clearance rate of ApoA1 protein or is the result of increased intestinal synthesis of ApoA1.